DHA-enriched phosphatidylcholine suppressed angiogenesis by activating PPARγ and modulating the VEGFR2/Ras/ERK pathway in human umbilical vein endothelial cells

Docosahexaenoic acid-enriched phosphatidylcholine (DHA-PC) is a new generation of omega-3 lipids, which contains an ester bond linking DHA at the sn-2 position of phospholipid. DHA-PC has become the interest recently as its better bioavailability and anti-oxidation capacity. In this study, the anti-angiogenic effect of DHA-PC was evaluated. The capacities of proliferation, migration, tube formation of human umbilical vein endothelial cells were significantly declined after DHA-PC treatment. Furthermore, DHA-PC inhibited the neovascularization of the chick chorioallantoic membrane in vivo. Mechanism results indicated that DHA-PC enhances the expression of Peroxisome Proliferator-activated Receptor γ (PPARγ) at transcriptional and translational level, subsequently down-regulates the VEGFR2 expression and VEGFR2-mediated downstream Ras/ERK pathway, resulting in significant reduction in proliferation and differentiation. Additionally, PPARγ-specific antagonist GW9662 partly reversed the inhibition effects of DHA-PC on tube formation and neovascularization, suggesting that DHA-PC exerts anti-angiogenesis effect through activating PPARγ. These findings indicated that DHA-PC has a great prospect of anti-tumor angiogenesis therapy.

Angiogenesis; DHA-PC; Neovascularization; PPARγ; Tube formation.